NUCLEOTIDES-INDUCED CYTOSOLIC CALCIUM TRANSIENT AND PLASMA-MEMBRANE PERMEABILITY IN CHANG HUMAN LIVER-CELLS

Extracellular nucleotides induce changes in cytosolic free Ca2+ and al so increase plasma membrane permeability to Ca++ ions in Chang human l iver cells. Ca++ permeability induced by nucleotides is reversible and inactivated immediately upon removal of agonist. Stimulated cells tra nsferred into the fresh medium and re-exposed to nucleotides demonstra te reopening of Ca++ channel without stimulation of Ca++ transient. Re lative potencies of nucleotides to induce membrane permeability and Ca ++ transient were: UTP > ATP > gamma-S-ATP > ADP (non-hydrolyzable ATP analogues and AMP had no effect). The permeability is not affected by specific inhibitors of voltage-operated calcium channels (verapamyl,c is-diltiazem and nifedipin). Nucleotides do not produce plasmamembrane damages at concentrations up to 1 mM, as shown by exclusion of the pr opidium iodide. There are at least two types of nucleotides receptors in Chang cell membrane: P-2y subtype receptors which is responsible fo r generation of the Ca++ transient, and P-2x subtype receptors which l ead to the opening of plasma membrane Ca++ channels upon activation.